Pancreatic cancer ranks as one of the most lethal cancers in the developed world. In North America, it was estimated that of the new 45,220 cases of pancreatic cancer diagnosed in 2013, there will 38,460 deaths in the same year. In the UK, despite the improvements in the survival rates of certain cancers such as breast, bowel, ovarian, and non-Hodgkin's lymphomas, there has been little improvement in the survival rates of pancreatic cancer patients, with less than 3% of people surviving the disease beyond five years. Lack of early clinical markers and the asymptomatic nature of the disease contribute to late diagnosis. Consequently, by the time of diagnosis, surgical intervention at present the only option that will significantly extend life expectancy will usually not be a viable option due to the advanced stage of the disease. Surgery followed by chemotherapy, radiation therapy, or combinations of both, are currently the treatment options available. Such interventions however only offer a modest extension of lifespan, and recurrence is often high highlighting the urgent need for investigations into new targets.
S100P is a calcium-binding protein that is highly expressed in pancreatic cancer in the early stages. It binds to the receptor for advanced glycation end-products (RAGE) extracellularly and promotes cell proliferation, migration, invasion and survival. Its absence in pancreatitis, a condition which pancreatic cancer is sometimes misdiagnosed as, makes it an ideal clinical marker for early detection of the cancer. In addition, the protein has been validated as a druggable target in pancreatic cancer. Cromolyn, an anti-allergy drug has been shown to bind to S100P and inhibit its binding to RAGE in in vitro studies. Cromolyn is however not a viable therapeutic agent due to its low bioavailability—it is quickly excreted from the body after administration. A close analogue, 5-methyl cromolyn, was recently shown to be more efficient in inhibiting S100P/RAGE function than cromolyn—100 nmol/L compared to the latter's 10 μM/L in in vitro studies. A need exists for further therapeutic agents for inhibiting S100P/RAGE function.